1. Carbon-Carbon Bond Forming Reactions
Chapter 26 Topics:
Organocuprate Coupling.
R-X + (R')2CuLi
Suzuki Coupling.
R-X + Organoborane
Heck Reaction.
R-X + Alkene
Dihalocarbene addition.
:CX2 + Alkene
Simmons-Smith Reaction.
ICH2ZnI + Alkene

2. Carbon-Carbon Bond-Forming Reactions in Organic Synthesis
Coupling Reactions of Organocuprates:
Recall that organocuprate reagents react a variety of functional compounds including acid chlorides, epoxides and ,-unsaturated carbonyl compounds.
Organocuprate reagents also react with organic halides R'—X to form coupling products R—R' that contain a new C—C bond.
Only one R group of the organocuprate is transferred to form the product, while the other becomes part of the RCu, a reaction product.

3. Carbon-Carbon Bond-Forming Reactions
Coupling Reactions of Organocuprates:
Methyl, 1°, cyclic 2°, vinyl and aryl halides can be used. Reactions with vinyl halides are stereospecific.
The halogen (X) may be Cl, Br or I.
Tertiary (3°) halides are too sterically hindered to react.

4. Carbon-Carbon Bond-Forming Reactions
Coupling Reactions of Organocuprates:
Since organocuprate reagents are prepared in two steps from alkyl halides (RX), this method ultimately converts two organic halides (RX and R'X) into a hydrocarbon R—R' with a new carbon—carbon bond.
Note that this means that using this methodology, a given hydrocarbon can often be made by two different routes.

5. Carbon-Carbon Bond-Forming Reactions
The Suzuki Reaction: General
The Suzuki reaction is a palladium-catalyzed coupling of a vinyl or aryl halide (R'X) with an organoborane (RBY2) to form a product (R—R') with a new C—C bond.
Pd(PPh3)4 is the typical palladium catalyst.
The reaction is carried out in the presence of a base such as NaOH or NaOCH2CH3.
The halogen is usually Br or I.
The Suzuki reaction is completely stereospecific.

6. Carbon-Carbon Bond-Forming Reactions
The Suzuki Reaction: Uses a Pd Catalyst
Organopalladium compounds are compounds that contain a carbon—palladium bond.
During a reaction, Pd is coordinated to a variety of groups called ligands, which donate electron density to (or sometimes withdraw electron density from) the metal.
A common electron donating ligand is phosphine, some derivatives of which are shown:

7. Carbon-Carbon Bond-Forming Reactions
The Suzuki Reaction:
A general ligand bonded to a metal is often designated as “L.” Pd bonded to four ligands is denoted as PdL4.
Organopalladium intermediates are generally prepared in situ during the course of a reaction, from another palladium reagent such as Pd(OAc)2 or Pd(PPh3)4. Note that “Ac” is the abbreviation for the acetyl group, CH3C=O, so OAc is the abbreviation for CH3CO2¯.
Usually only a catalytic amount of Pd reagent is used.
Two common processes, called oxidative addition and reductive elimination, dominate many reactions of palladium compounds.

8. Carbon-Carbon Bond-Forming Reactions
The Suzuki Reaction: A Reaction with a Pd Catalyst

9. Carbon-Carbon Bond-Forming Reactions
The Suzuki Reaction:

10. Carbon-Carbon Bond-Forming Reactions
The Suzuki Reaction: The boranes
The organoboranes used in the Suzuki reaction are acquired from two sources.
Vinylboranes, which have a boron atom bonded to a carbon—carbon double bond, are prepared by hydroboration using catecholborane, a commercially available reagent.
Hydroboration adds H and B in a syn fashion to form a trans vinylborane. With terminal alkynes, hydroboration always places the boron atom on the less substituted terminal carbon.

11. Carbon-Carbon Bond-Forming Reactions
The Suzuki Reaction: The boranes
Arylboranes, which have a boron atom bonded to a benzene ring, are prepared from organolithium reagents by reaction with trimethyl borate [B(OCH3)3]

12. Carbon-Carbon Bond-Forming Reactions
The Suzuki Reaction: Mechanistic Details

13. Carbon-Carbon Bond-Forming Reactions
The Heck Reaction:
The Heck reaction is a Pd-catalyzed coupling of a vinyl or aryl halide with an alkene to form a more highly substituted alkene with a new C—C bond.
Palladium(II) acetate [Pd(OAc)2] in the presence of a triarylphosphine [P(o-tolyl)3] is the typical catalyst.
The reaction is carried out in the presence of a base such as triethylamine.
The Heck reaction is a substitution in which one H atom of the alkene starting material is replaced by the R' group of the vinyl or aryl halide.

14. Carbon-Carbon Bond-Forming Reactions
The Heck Reaction:
The alkene component is typically ethylene or a monosubstituted alkene (CH2=CHZ).
When Z = Ph, COOR or CN in a monosubstituted alkene, the new C—C bond is formed on the less substituted carbon to afford a trans alkene.
The halogen is typically Br or I.
When a vinyl halide is used as the organic halide, the reaction is stereospecific.

15. Carbon-Carbon Bond-Forming Reactions
The Heck Reaction:

16. Carbon-Carbon Bond-Forming Reactions
The Heck Reaction: Retrosynthesis
To use the Heck reaction in synthesis, you must determine what alkene and what organic halide are needed to prepare a given compound.
To work backwards, locate the double bond with the aryl, COOR, or CN substituent, and break the molecule into two components at the end of the C=C not bonded to one of these substituents.

17. Carbon-Carbon Bond-Forming Reactions
The Heck Reaction:

18. Carbon-Carbon Bond-Forming Reactions
Carbenes and Cyclopropane Synthesis:
A carbene, R2C:, is a neutral reactive intermediate that contains a divalent carbon surrounded by six electrons: the lone pair, and two each from the two R groups.
These three groups make the carbene carbon sp2 hybridized, with a vacant p orbital extending above and below the plane containing the C and the two R groups.
The lone pair occupies an sp2 hybrid orbital.

19. Carbon-Carbon Bond-Forming Reactions
Carbenes and Cyclopropane Synthesis:
Dihalocarbenes, :CX2, are especially useful reactive intermediates since they are readily prepared from trihalomethanes (CHX3) by reaction with strong base, e.g., treatment of chloroform (CHCl3) with KOC(CH3)3 forms dichlorocarbene, :CCl2.
Dichlorocarbene is formed by a two-step process that results in the elimination of the elements of H and Cl from the same carbon.
Loss of the two elements from the same carbon is called  elimination.

20. Carbon-Carbon Bond-Forming Reactions
Carbenes and Cyclopropane Synthesis:

21. Carbon-Carbon Bond-Forming Reactions
Carbenes and Cyclopropane Synthesis:
Since dihalocarbenes are electrophiles, they readily react with double bonds to afford cyclopropanes, forming two new carbon—carbon bonds.

22. Carbon-Carbon Bond-Forming Reactions
Carbenes and Cyclopropane Synthesis:
Carbene addition occurs in a syn fashion from either side of the planer double bond.
Carbene addition is a stereospecific reaction, since cis and trans alkenes yield different stereoisomers as products.
Cyclopropanation is a concerted reaction, so both bonds are formed in a single step.

23. Carbon-Carbon Bond-Forming Reactions
The Simmons-Smith Reaction:
Nonhalogenated cyclopropanes can be prepared by the reaction of an alkene with diiodomethane, CH2I2, in the presence of a copper-activated zinc reagent called zinc-copper couple [Zn(Cu)]. This is known as the Simmons-Smith reaction.
The reaction is stereospecific.

24. Carbon-Carbon Bond-Forming Reactions
The Simmons-Smith Reaction: